1. Field of the Invention
The present invention relates to a method for producing a biochemical analysis unit, and particularly to a method for producing a biochemical analysis unit which prevents to cause a noise when a labeling substance or a fluorescent substance radiates or emits a light.
2. Description Related to the Prior Art
As disclosed in Japanese Patent Publications No. 1-60784, 1-60782, and 4-3952, an auto radiography image analyzing system is known for detecting a radioactive labeling substance which are dosed with a living organism. In the auto radiography image analyzing system, a part of the living organism on dosage of the labeling substance is used as a sample. When the sample overlaps for a predetermined time with a stimulable phosphor sheet having a stimulating phosphor layer, the energy of radiation irradiated from the radioactive labeling substances is accumulated and recorded in the stimulable phosphor layer. Thereafter when the stimulable phosphor layer is scanned in an electromagnetic wave, the stimulable phosphor is excited, and a stimulation light emitted from the stimulable phosphor layer is photoelectrically detected. Thus a detection data is obtained and effected in image processing for forming an image on a display, such as a CRT or the like, or a recording material.
In the auto radiography image analyzing system, a development processing is not necessary. Further the image data obtained from the detection data can be processed to reproduce a desired image and therefore a quantity analysis becomes possible with a computer.
Further, recently, an analyzing system is known for analyzing a substances derived from living organism, for example, a nucleic acid (such as DNA and RNA), proteins and the like. In the analyzing system, the substance derived from living organism that is labeled with a labeling substance is set in the electromagnetic waves for exiting the labeling substance. Thus the excited light is generated and detected such that the detecting data is obtained to form the image.
As the analyzing system, there are a fluorescent analyzing system, a chemiluminescence analyzing system and the like.
In the fluorescent analyzing system is carried out the determination of genetic sequence, expression level of gene, routs of metabolism, absorbance and discharge, the separation or the identification of protein, the estimation of molecular weight or properties of protein, or the like. The substance derived from living organism, such as protein, is labeled with the fluorescent substances by dipping a gel support in a solution containing a fluorescent substance after the gel support on which a plurality of proteins are distributed by means of electrophoresis. When the sample is excited with the exciting light, then a fluorescent light generated from the fluorescent substance is detected to form an image. Thus positions and amount distributions of proteins on the gel support can be known. The fluorescent analyzing system has a merit in that the radioactive substance is not used, and that the genetic sequence and the like are easily determined.
In the fluorescent analyzing system, a western blotting method and a southern blotting method may be used. In the western blotting method, a part of proteins after electrophoresis is transferred to a solid base such as nitrocellulose sheet from the gel support. Then, an antibody which makes a selective reaction with the substance of living organism to be detected is labeled with the labeling substance such as fluorochrome to produce a probe. When the probe and the protein are combined, the protein is selectively labeled. The positions or the quantitative distribution of protein on the solid base can be detected by sensing a fluorescent light from the fluorochrome which is excited with exciting light. The western blotting method is also used for searching a distribution of DNA in a DNA segment.
In the southern blotting, after a plurality of DNA fragments on a gel support is distributed by means of electrophoresis and denaturated, at least a part of DNA fragments is transferred onto a transfer support such as nitrocellulose support. The denaturated DNA fragments are hybridized with a probe in which a fluorescent dye labels DNA or RNA complementary to the denaturated DNA fragments. In the hybridization, only the target DNA fragments are selectively labeled. When the fluorescent dye is excited, then the distribution of the target DNA on the transfer support is detected. Further, it is preferable to use the enzyme. In this case, the comprementary DNA is combined with the enzyme, and contacted to the fluorescent substrate, and the fluorescent substrate is transformed to the fluorescent substance. Then the fluorescent light irradiated from the fluorescent substance is sensed to detect the distribution of the target DNA.
In the chemiluminescent analyzing system, the labeling substance is used, which generates a visible chemiluminescent light by contacting to the chemiluminescent substrate. The substance fixed on a support is selectively labeled with the labeling substance, and thereafter contacted to the chemiluminescent substrate to emit the chemiluminescent light which is photometry detected.
Recently, there is known a micro array analyzing system. In the micro array analyzing system, a specific binding substance is used, which can be bound with the substance derived from living organism, such as hormone, tumor marker, enzyme, antibody, antigen, abzyme, other protein, nucleic acid, cDNA, DNA, RNA or the like. According to the specific binding substance are established sequence, base length, composition and the like.
In the micro array analyzing system, the several substances labeled with a labeling substance are spotted at different positions on a surface (glass plate, porous membrane and the like) of the biochemical analysis unit. The substances are combined with the specific binding substance previously spotted by a spotting device, and labeled with the labeling substance or the luminescent substance for producing the micro array. When the exciting light is irradiated, a light (such as luminescence) is generated by a labeling substance in the micro array and photoelectrically detected.
Further, an improvement of the micro array is used with the radioactive labeling substance for labeling the substance of living organism that is bounded with the specific binding substance. The micro array is superposed on the stimulable phosphor sheet to make an exposure of the stimulating phosphor layer. Then the exciting light is impinged on the stimulating phosphor layer, and the stimulation light emitted from the stimulating phosphor layer is photoelectrically detected.
According to the micro array image analyzing system, several sorts of the specific binding substance are formed as spots in high density. After labeled with the labeling substance, the substance derived from living organism is dropped on the spots to hybridize with the specific binding substance. Thus the analysis of the substance derived from the living organism is made in a short time.
In the above mentioned image analyzing system for micro array is used a biochemical analysis unit in which a micro array is formed on a support (or base), such as a glass plate, a membrane or the like. The micro array has plural spots for detecting plural kinds of materials. However, in the biochemical analysis unit as the electromagnetic wave or the light generated from the labeling substance in the neighboring spots is mixed, noises are caused in the detection data. In this case, if the radioactive labeling substance is used, for example, the quantitative analysis of the substance derived from living organism is not made correctly. Especially, if the labeling substance is spotted in high density, the quantitative analysis becomes simply bad.
Note that in order to make the cost for producing the biochemical analysis unit lower, it is preferable to produce the biochemical analysis unit effectively.